Background & Aims of the Study: In this research, Long-Term Hydrologic Impact Assessment model is selected for simulation of runoff and NPS pollution. The aim of this study is modeling of non-point source pollution by L-THIA model in Zayandehrood watershed in 2015. Materials & Methods: In this study, analytical survey and investigation of references in the context of library studies has been used. Zayandehrood watershed is located in Esfahan, Iran. Required data in this study are land use, soil and precipitation data from studied period. The first L-THIA model run and then the spatial distribution of non-point source pollution analysed within the study area. The annual average runoff volume, depth and the non-point source nitrogen and phosphorus load and the spatial distribution were estimated. Results: According to the study, we concluded that amount of nitrogen and phosphorus load in agricultural and residential areas are more serious and the nitrogen load due to nonpoint source pollution was larger than phosphorus load in Zayandehrood basin. The maximum runoff depth in the region was calculated 501.371 cm and the maximum nonpoint source pollution obtained 24244.27 kg. The results indicated the watershed likely is affected to impacts from urbanization and agriculture. Conclusions: The results of this study can be used for urban planning and decision making in an effort to protect water and habitat quality of Zayandehrood river. Integration of introduced model and other hydrologic models can be increased accuracy and precision of results. Also, sub-watersheds can prioritize for watershed management in in the vulnerable sections.